{
  "abstract": "Abstract Objective To evaluate the efficacy and safety of anrikefon (formerly known as HSK21542), a novel selective peripherally restricted kappa opioid receptor agonist, in patients with chronic kidney disease associated pruritus.Design Multicentre, double blind, randomised placebo controlled phase 3 trial.Setting 50 centres in China, June 2022 to June 2024.Participants 652 patients with moderate to severe CKD associated pruritus undergoing haemodialysis were screened: 545 were randomly assigned (1:1 ratio) to receive either anrikefon (n=275) or placebo (n=270).Interventions Intravenous anrikefon (0.3 μg/kg body weight) or placebo three times weekly for 12 weeks, followed by an optional open label extension phase with anrikefon treatment for 40 weeks.Main outcome measures The primary endpoint was the percentage of patients achieving at least a 4 point reduction in weekly mean 24 hour worst itching intensity numerical rating scale (WI-NRS) score from baseline to week 12. Secondary outcomes were the percentage of patients achieving at least a 3 point reduction in weekly mean WI-NRS score from baseline to week 12, as well as changes in itch related quality of life from baseline using the Skindex-10 and 5-D itch scales. The change in itch related quality of life from baseline to week 40 of open label treatment was also reported using the 5-D itch scale. The safety of anrikefon was evaluated throughout the trial.Results 243/275 (88%) patients in the anrikefon group and 254/270 (94%) in the placebo group completed the 12 week double blind treatment. 443 subsequently entered the 40 week open label extension phase. 37% of patients in the anrikefon group showed at least a 4 point reduction in WI-NRS score at week 12 compared with 15% in the placebo group (P<0.001). The percentage of patients with at least a 3 point reduction in WI-NRS score from baseline to week 12 was 51% in the anrikefon group compared with 24% in the placebo group (P<0.001). The anrikefon group showed significant improvements in itch related quality of life (mean change from baseline in 5-D itch scale −5.3 v −3.1, P<0.001 and in Skindex-10 scale −15.2 v −9.3, P<0.001). Anrikefon also showed sustained long term efficacy during the open label extension phase at week 40, with persistent improvement in quality of life scores on the 5-D itch scale. Mild to moderate dizziness was more common in the anrikefon group than placebo group but without evident clinical consequences.Conclusions In patients with moderate to severe pruritus undergoing haemodialysis, anrikefon was found to be safe and resulted in a noticeable reduction in itch intensity and an improvement in itch related quality of life.Trial registration ClinicalTrials.gov NCT05135390.",
  "authors": [
    {
      "affiliations": [
        "Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China"
      ],
      "name": "Bi-Cheng Liu"
    },
    {
      "affiliations": [
        "Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China"
      ],
      "name": "Zuo-Lin Li"
    },
    {
      "affiliations": [
        "Kidney Disease Centre, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China"
      ],
      "name": "Ping Zhang"
    },
    {
      "affiliations": [
        "Department of Nephrology, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi, China"
      ],
      "name": "Ai-Min Zhong"
    },
    {
      "affiliations": [
        "Department of Nephrology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China"
      ],
      "name": "Ya-Ling Bai"
    },
    {
      "affiliations": [
        "Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China"
      ],
      "name": "Yan Xu"
    },
    {
      "affiliations": [
        "Department of Nephrology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China"
      ],
      "name": "Bi-Hu Gao"
    },
    {
      "affiliations": [
        "Department of Nephrology, Zhongshan Traditional Chinese Medicine Hospital, Zhongshan, Guangdong, China"
      ],
      "name": "Yan-Lin Li"
    },
    {
      "affiliations": [
        "Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China"
      ],
      "name": "Yu Wang"
    },
    {
      "affiliations": [
        "Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Ling-Hui Zhou"
    },
    {
      "affiliations": [
        "Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China"
      ],
      "name": "Li Yao"
    },
    {
      "affiliations": [
        "Blood Purification Centre, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China"
      ],
      "name": "Jun-Xia Wang"
    },
    {
      "affiliations": [
        "Department of Nephrology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China"
      ],
      "name": "Rui Yan"
    },
    {
      "affiliations": [
        "Department of Nephrology, Wuxi People’s Hospital, Wuxi, Jiangsu, China"
      ],
      "name": "Liang Wang"
    },
    {
      "affiliations": [
        "Department of Nephrology, The First People’s Hospital of Nanning, Nanning, Guangxi, China"
      ],
      "name": "Bing Liao"
    },
    {
      "affiliations": [
        "Department of Nephrology, Yibin Second People’s Hospital, Yibin, Sichuan, China"
      ],
      "name": "De-Qiong Xie"
    },
    {
      "affiliations": [
        "Department of Nephrology, Yueyang People’s Hospital, Yueyang, Hunan, China"
      ],
      "name": "Xiang-Ming Yi"
    },
    {
      "affiliations": [
        "Department of Nephrology, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China"
      ],
      "name": "Tian-Jun Guan"
    },
    {
      "affiliations": [
        "Department of Nephrology, The First Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, China"
      ],
      "name": "Cai-Li Wang"
    },
    {
      "affiliations": [
        "Department of Nephrology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China"
      ],
      "name": "Gui-Sen Li"
    },
    {
      "affiliations": [
        "Department of Research and Development of Haisco Pharmaceutical Group, Chengdu, Sichuan, China"
      ],
      "name": "Fang-Qiong Li"
    },
    {
      "affiliations": [
        "Kidney Disease Centre, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang, China"
      ],
      "name": "Jiang-Hua Chen"
    },
    {
      "affiliations": [],
      "name": "on behalf of the Anrikefon-302 study collaborator group"
    }
  ],
  "title": "Efficacy and safety of anrikefon in patients with pruritus undergoing haemodialysis: multicentre, double blind, randomised placebo controlled phase 3 trial",
  "uid": "7ad5f754-ddbd-5673-8841-25a02cd68c89"
}